It is strongly suggested that oncogenes transform cells through a common pathway, which perhaps involves most of the cellular growth regulatory systems including cell-cell recognition coupled to growth control, growth factor production and cell cycle controls. In attempting to elucidate this pathway, we have initiated studies to molecularly clone and characterize cellular genes whose activation leads to induction of full or partial transformed phenotypes in cells, by employing the cDNA expression system we recently developed. The approach comprises the following steps: 1) construction of a cDNA clone expression library with the mRNA from SV40-transformed human fibroblast; 2) transduction of the library into NIH3T3 cells; 3) screening of colonies that show lack of growth contact inhibition; 4) recovery of the integrated cDNA into E. coli for characterization. Transfection of 10 million NIH3T3 cells with the library (l.5 x l million) independent clones) yielded 62 colonies that showed lack of contact inhibition: 36 are perhaps transformed by integrated cDNA, 24 by spontaneous transformation, and 2 by SV40 T-antigen. The integrated cDNAs from the 36 colonies are being recovered into E. coli for characterization. One cDNA clone recovered is able to induce the same transformed phenotype in NIH3T3 cells but has no detectable hemology to the major know oncogenes.